Apolipoprotein B100 as Protective Biomarker in AMD

Article: Study Finds Up to 30% of Patients with Wet Macular Degeneration Can Safely Stop Eye Injections
Source: Johns Hopkins Medicine
Published: January 18, 2022

Venn diagram of 172 key proteins in AMD

Age-related macular degeneration (AMD) is the leading cause of blindness in individuals 50 years of age and older. "Wet" AMD, characterized by neovascularization and fluid leaking from blood vessels onto the retina, is the more severe form leading to most cases of vision loss. Current therapy consists of anti-vascular endothelial growth factor (anti-VEGF) injections monthly or every other month. Although effective at slowing progression and preventing vision loss, the method and frequency of therapy often present obstacles to patient adherence. Researchers sought to investigate the outcome of pausing anti-VEGF therapy, following 106 patients with wet AMD over a two-year study period; the patients themselves were treated by the research team from 2013 to 2020. Each patient underwent a customized anti-VEGF injection schedule, wherein the lead clinician determined whether the patients needed another injection at each visit or if they could enter a treatment pause. Eyes without treatment that showed no signs of fluid accumulation or advancing vision loss after at least 30 weeks of monitoring were considered safely weaned off anti-VEGF therapy. At the end of one year, 38 of 122 (31%) of treated eyes, or one-third of the patients, had stopped anti-VEGF therapy in at least one eye. Half of the patients, or 63 of 122 (52%) treated eyes, required injections only every 6–12 weeks, with a handful being weaned off of treatment at the end of year two. Patients who could pause therapy showed better outcomes. The lead clinician comments, "Across the board, the patients who could enter a treatment pause did the best even though they were receiving no anti-VEGF drugs. They had better visual acuity, better gain of vision and less fluid in their retina."

The investigators next looked at biomarkers that distinguished the patients who could be weaned off of treatment from those who required monthly injections to maintain their vision. Fluid samples from some of the patients, collected before the treatment plan and at subsequent visits, showed differences in the amounts of 172 proteins between the two groups. The researchers chose one protein, apolipoprotein B100, to study in further detail; apolipoprotein B100 had been demonstrated in other studies to be a part of drusen, deposits that accumulate under the retina and contribute to dry AMD. They found that apolipoprotein B100 was present in much higher levels in the eyes of patients who could be weaned off of anti-VEGF and also present in higher levels in patients who did not develop wet AMD compared to those that did, leading them to think that apolipoprotein B100 has a protective effect against wet AMD. This hypothesis was confirmed when mice genetically engineered to have higher levels of apolipoprotein B100 showed less abnormal blood vessel growth in the retina than mice with lower levels of the protein. Although apolipoprotein B100 was chosen as a proof-of-concept, the researchers add that other proteins could have similar protective effect and potential as therapeutic candidates. This being said, the lead clinician stresses that randomized clinical trials in a large group of patients with wet macular degeneration must happen before broader recommendations on pausing anti-VEGF therapies can be developed.

My rating of this study: ⭐⭐⭐

Cao X, Sanchez JC, Dinabandhu A, et al. "Aqueous proteins help predict the response of patients with neovascular age-related macular degeneration to anti-VEGF therapy." Journal of Clinical Investigation.  7 December 2022. https://doi.org/10.1172/JCI144469